Assisted Reproduction and Infertility
testing (PGT). PGT is a technique in which genetic testing is performed on a biopsy from a pre-implantation-stage embryo to ensure that only embryos free of the specific assayed mutation are transferred back to the uterus.78
PGT has been used to screen for several cancer predisposition syndromes, including adenomatous polyposis of the colon (APC), neurofibromatosis type 2 (NF2). and inherited breast cancer (BRCA1 and BRCA2).79
It is encouraging that children born to cancer
survivors are not at increased risk for malformations or death compared with women without a cancer history;80
increased risk for low birth weight and prematurity.80
Measures Exist to Assess Reproductive Function Pre- and Post-cancer Therapy
Ovarian reserve is defined as the functional potential of the ovary and reflects the number and quality of oocytes within the ovary.81
Being able to
measure the ovarian reserve in an oncofertility setting is beneficial because doing so pre-cancer treatment can help predict how vulnerable a patient may be to cancer therapies and could dictate the need for fertility preservation options. Testing the ovarian reserve post-cancer therapy may indicate whether a potential for restored natural fertility exists or whether the patient must rely on previously performed fertility preservation methods. Although there is no single predictive marker of ovarian reserve, several tests have been developed (see Table 1).
Currently, serum anti-Müllerian hormone (AMH) levels combined with antral follicle count (AFC) serve as the most robust markers for evaluating ovarian reserve.82,83
the granulosa cells in developing ovarian follicles.84,85
AMH is a hormone that is produced by AMH levels are
not affected by menstrual cycle day, oral contraceptive use, or pregnancy.84
A study that was performed in regularly menstruating women to test several hormonal markers of aging suggests that serum AMH is the most accurate marker in predicting the occurrence of the menopausal transition within four years.88
In addition to a woman’s age, serum AMH is also correlated inversely with the number of antral follicles, which can be determined by counting the number of 2–10 mm-diameter follicles using transvaginal ultrasound.87,89
been well established in clinical studies.89–91
During natural aging, serum AMH levels decrease rapidly after 37 years, and this drop precedes but is related to the onset of menopause.86,87
however, they may be at
The results of this study demonstrated that, although the breast cancer patients had normal ovarian reserve prior to cancer treatment, post-treatment a significant decrease in AFC and a drastic reduction in AMH levels occurred. Being able to correlate markers such as serum AMH levels and AFC with a diminished ovarian reserve is critical in the fertility preservation decision-making process. Performing these tests helps to assess the need for fertility intervention in patients who may be susceptible to early menopause or a decreased ovarian reserve both before and after treatment.
were compared between regularly menstruating breast cancer patients (22–42 years of age) and their non-cancer patient counterparts.95
Although these tests are an appropriate measure of the remaining developing follicle pool, it is important to remember that they do not guarantee that pregnancy, the ultimate proof of fertility, will occur.81–83 While AMH plus AFC is one of the better combinations for prediction of ovarian reserve, a variety of other tests are commonly used to evaluate a woman’s fertility status (see Table 1).59,83
For example, additional
hormonal assays include tests of day 3 estradiol, FSH, and inhibin B. Dynamic tests such as the clomiphene citrate challenge test can also be used to test a patient’s ability to ovulate. It is also of critical importance to counsel patients that a return to normal menstruation is not necessarily indicative of fertility, because there is still a possibility of anovulation or diminished ovarian reserve.96,97
Conclusion
Common cancer treatments have the potential to disrupt all parts of the female reproductive axis, thus leaving patients with side effects such as premature menopause or infertility. A threat to fertility on top of a cancer diagnosis can be devastating and greatly reduce a patient’s quality of life. Self-efficacy, which is defined as the extent to which an individual believes in his or her ability to organize and execute courses of action competently, greatly influences a young adult’s ability to deal with the challenges of cancer and maintain a positive quality of life.3
A patient’s confidence in his
or her ability to acquire and understand medical information accurately contributes to overall self-efficacy. A recent online survey of young adult cancer patients demonstrated that more than 65 % had used or wanted information about infertility and options for having children.98,99
A strong correlation between AMH levels and AFC has The number of small antral
follicles is one of the best correlates to ovarian age with representation to ovarian reserve.89
It has also been shown that serum AMH levels and AFC, when analysed together, are indicative of primordial follicle number independent of age.92
Thus, it can be gathered that, in
combination, serum AMH levels and AFC are strong correlates to ovarian age and the remaining ovarian reserve.
The use of serum AMH levels and AFC to test ovarian reserve has been effectively translated into the oncofertility setting, where various cancer treatments have been shown to compromise the follicle pool.93,94
Clinical studies have shown that serum AMH levels and AFC measured in cancer patients post-treatment were highly correlated to each other and significantly lower than in control non-cancer counterparts.23,91
In a recent longitudinal study, AFC, ovarian volume and levels of FSH, LH, estradiol, inhibin A and B, activin A, and AMH
32
Oncofertility is an interdisciplinary field that was developed not only to explore and expand fertility preservation options for cancer patients but also to increase patient awareness of these options. Oncofertility requires a team-based approach to clinical care. In healthcare, a team is defined as a group of professionals who interact dynamically, interdependently, and adaptively toward the shared goal of assessing, planning, or carrying out patient care.100
At the simplest level, an
oncofertility team consists of oncologists working closely with reproductive endocrinologists to define and implement the best treatment plan for the patient. In settings with established oncofertility programs, the team may be broader and include nurses, social workers, clinical psychologists, and patient navigators who help guide the patient through the fertility preservation process.101
As a PCP, the gynecologist also has the potential to be an essential part of an oncofertility team. Gynecologists are in a unique position because they are likely to interact with patients faced with a cancer diagnosis
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